It is now well-established that nutritionally stressful early environments can set up the transgenerational transmission of lower birth weight in offspring, which in turn sets that individual on a compromised lifecourse health and functional trajectory. This research is highlighting an important means by which social inequality gets "under the skin", and may even be transmitted across generations. Most of this work has used birth weight records as a proxy for maternal-gestational conditions, and as such, the pathways that might account for the transgenerational transmission of inequality are poorly understood. The placenta, as the mediator of maternal nutrition and fetal growth, is a good candidate mechanism. We currently have NSF support for 3 years of new fieldwork with our large birth cohort in the Philippines, which will track new pregnancies in the original cohort members (now young adults) and collect birth weights and other information on their newborn offspring (generation 3). The intent of this R03 is to piggy back a field test and pilot analysis of placental collection onto this study. All young mothers targeted in this proposal are original birth cohort members in the Cebu Longitudinal Health and Nutrition Survey (CLHNS), a large population-based multi-generational study in the Philippines that has followed the same group of individuals since their mothers were pregnant with them 26 years ago. As these original cohort members are now of child-bearing age, we have a unique opportunity to use the rich longitudinal nutritional histories available for each young mother to evaluate an important candidate mechanism for the transmission of health inequality to their newborn offspring. We will collect 30 placentas from women selected from the extremes of the original birth cohort's birth weight distribution in order to troubleshoot collection, processing, and shipping protocols, to allow preliminary tests of our hypotheses, and to generate data to allow calculation of effect sizes for power calculations when designing an R01 to continue follow up of generation 3 newborns. Although the strength of the Cebu Study is its rich, longitudinal and multi-generational design, our team includes expertise that will allow evaluation of the key candidate placental processes that could be involved in transgenerational transmission between mother and offspring, including changes in morphometry and epigenetic changes that could modify expression of genes that regulate fetal growth. Our ultimate goal is to justify an expanded study of the transgenerational transmission of health inequality via gestational pathways in the Cebu cohort. Adding a placental component to an already robust longitudinal record of panel data promises important insights into the processes that underlie variation in birth weight, and by extension, the many adult outcomes downstream of birth weight. PUBLIC HEALTH RELEVANCE: New evidence suggests that the impact of social inequality on health can transcend the present generation and even influence health and well-being in offspring. This study proposes to study how a woman's health and nutritional history influence fetal growth via effects on the placenta, which serves as the interface between the mother and fetus. The proposed study would be the first to explore these questions in mothers who have been followed continuously since prior to their own births, when their pregnant mothers (the grandmothers) were first enrolled in 1983.